Background: Plumbago zeylanica Linn. (Chitrak) is a traditional medicinal herb in the Ayurvedic pharmacopoeia, valued for its anticancer, anti-inflammatory, and antimicrobial properties. While plumbagin, the principal bioactive naphthoquinone from this plant, has been extensively investigated, other phytoconstituents including chitranone and droserone remain largely unexplored as potential anticancer candidates. Objective: This study aimed to evaluate the anticancer potential of chitranone and droserone, two naphthoquinone derivatives from P. zeylanica, against the epidermal growth factor receptor (EGFR) kinase domain (PDB ID: 8A2B) using molecular docking and ADMET prediction, with doxorubicin as a reference standard. Methods: Phytoconstituents were identified from the IMPPAT database. The EGFR kinase domain crystal structure (resolution: 1.69 Å) was validated via Ramachandran plot analysis using PROCHECK. Molecular docking was performed using Auto Dock Vina 1.5.6. Binding interactions were visualized using Discovery Studio and PyRx. ADMET profiling was conducted using Swiss ADME and ProTox-II. Results: Chitranone demonstrated the highest binding affinity (−10.5 kcal/mol) with three hydrogen bonds and 16 total interactions, surpassing doxorubicin (−8.8 kcal/mol, four hydrogen bonds, 11 interactions). Droserone showed a binding energy of −7.1 kcal/mol with one hydrogen bond and seven interactions. Both naphthoquinones exhibited zero Lipinski violations, high gastrointestinal absorption, and favorable drug-likeness. Chitranone had a predicted LD₅₀ of 1000 mg/kg (toxicity class 4) vs. 205 mg/kg (toxicity class 3) for doxorubicin. Conclusion: Chitranone exhibited superior binding affinity to the EGFR kinase domain compared to doxorubicin, suggesting its potential as a lead compound for anticancer drug development. Both naphthoquinones warrant further in vitro and in vivo validation.
Dr. Priyanka K. Dighde* (Sat,) studied this question.